Genomics of cellular proliferation in periodic environmental fluctuations
Living systems control cell growth dynamically by processing information from their environment. Although responses to a single environmental change have been intensively studied, little is known about how cells react to fluctuating conditions. Here, we address this question at the genomic scale by...
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Veröffentlicht in: | Molecular systems biology 2018-03, Vol.14 (3), p.e7823-n/a |
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Zusammenfassung: | Living systems control cell growth dynamically by processing information from their environment. Although responses to a single environmental change have been intensively studied, little is known about how cells react to fluctuating conditions. Here, we address this question at the genomic scale by measuring the relative proliferation rate (fitness) of 3,568 yeast gene deletion mutants in out‐of‐equilibrium conditions: periodic oscillations between two environmental conditions. In periodic salt stress, fitness and its genetic variance largely depended on the oscillating period. Surprisingly, dozens of mutants displayed pronounced hyperproliferation under short stress periods, revealing unexpected controllers of growth under fast dynamics. We validated the implication of the high‐affinity cAMP phosphodiesterase and of a regulator of protein translocation to mitochondria in this group. Periodic oscillations of extracellular methionine, a factor unrelated to salinity, also altered fitness but to a lesser extent and for different genes. The results illustrate how natural selection acts on mutations in a dynamic environment, highlighting unsuspected genetic vulnerabilities to periodic stress in molecular processes that are conserved across all eukaryotes.
Synopsis
Genome‐scale analysis of yeast fitness under periodic stress reveals how the selection of mutations can operate in dynamic environments. In oscillating environments, deviation from time‐average fitness is common, and numerous gene deletions confer hyperproliferation at short stress periods.
Two genomic screens are performed to address the question of fitness inhomogeneity (deviation from time‐average expectation) in periodic salt stress and periodic methionine availability.
Fitness is inhomogeneous for hundreds of genes, and these genes differ between the two surveys.
Fast salinity oscillations provide a profound fitness advantage to a subset of gene deletions.
Gene deletion mutants of the same pathway or with similar fitness alterations in steady conditions can largely differ in their response to dynamic conditions.
Graphical Abstract
Genome‐scale analysis of yeast fitness under periodic stress reveals how the selection of mutations can operate in dynamic environments. In oscillating environments, deviation from time‐average fitness is common, and numerous gene deletions confer hyperproliferation at short stress periods. |
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ISSN: | 1744-4292 1744-4292 |
DOI: | 10.15252/msb.20177823 |